Esca is one of the most widespread grapevine trunk diseases affecting vineyards. This complex disease leads to leaf alterations, wood necrosis and eventually to plant death. Esca symptoms are caused by several fungi inhabiting the xylem of host plants and degrading the wood structure. The main pathogens causing the disease are Phaeomoniella chlamydospora, Phaeoacremonium minimum, Fomitiporia mediterranea and other wood-rotting basidiomycetes. Grapevine susceptibility to esca can be predisposed by several factors, especially climate, vine age, and cultivar. An experiment was carried out (in 2015) to assess if esca expression on leaves could also be clone-dependent. Chardonnay clones 76 and 95 grown in the same plot were compared according to their developmental and physiological traits, metabolome, and foliar symptom expression. Leaves were sampled during summer on visually healthy vines as controls (C), and from asymptomatic (D-) and symptomatic (D+) shoots of esca-affected vines. Analysis of their metabolomes highlighted a clone-dependent metabolite fingerprint associated to esca expression. Opposite variations of specific metabolites were found between C and D+ leaves of both clones. The experiment was repeated (in 2018). Leaf samples could be discriminated, especially the C and D+ samples for each clone, but the differences were less marked than in the first experiment. Discriminant compounds were all different between the two experiments, and showed no opposite variations between C and D+ samples of both clones, which indicated variable metabolite responses from year to year for both clones. These results confirm that the leaf metabolite fingerprint associated to esca expression is clone-dependent, and is year-dependent in intensity and nature.